Dialysis-related amyloid arthropathy: MR findings in four patients

Dialysis-related amyloidosis is a recently recognized complication of long-term hemodialysis. It is caused by the deposition of a unique form of amyloid derived from circulating beta 2-microglobulin. This study describes the MR imaging characteristics in five articular sites of four symptomatic patients with biopsy-proved (three patients) or clinically and radiographically suspected (one patient) dialysis-related amyloidosis. Three wrists, one knee, and one cervical spine were examined. The extent of osseous and soft-tissue involvement at each joint site was well shown by MR imaging. Lesions that were apparently intraosseous on conventional radiographs were shown to be caused by well-defined erosions that extended to the articular surface. The MR signal characteristics of the amyloid deposition were intermediate between those of fibrocartilage and muscle on all sequences, distinguishing the deposition from cellular lesions or those containing large amounts of water, such as inflammatory masses, acute or chronic synovitis, and brown tumors of hyperparathyroidism. The intraarticular masses were associated with a moderate joint effusion in the large joint imaged, and small effusions were present in the wrist. Use of a fat-suppression sequence enhanced visualization of amyloid deposits within the wrist of one patient but provided no additional information in the knee of a second patient. Our experience suggests that MR imaging is well suited to showing the extent and distribution of articular disease in dialysis-related amyloidosis.     

透析相关性淀粉样变骨关节病的影像学表现(附28例分析)

目的分析透析相关性淀粉样变骨关节病的影像学表现,探讨其病理及影像学特点,总结不同影像学检查方法的应用价值。方法对28例长期血液透析、有骨关节改变的慢性肾衰患者的骨关节影像学资料进行回顾性分析,X线检查28例,CT检查28例,MRI检查15例,检查部位包括肩、膝、髋、腕及腰椎。结果 28例患者X线平片主要表现为骨质疏松17例、骨膜及关节软骨下骨吸收13例、关节面下囊样骨质破坏12例、骨质硬化5例、关节肿胀3例及关节旁软组织钙化13例。28例患者在CT上主要表现为骨质疏松28例、骨膜及关节软骨下骨吸收10例、关节面下囊样骨质破坏18例、骨质硬化8例、关节肿胀11例及关节旁软组织钙化17例。15例患者MRI主要表现为骨质疏松7例、骨膜及关节软骨下骨吸收2例、关节面下囊样骨质破坏11例、骨质硬化2例、关节肿胀6例、关节旁软组织钙化4例、关节软骨侵蚀破坏15例、滑膜增厚15例及肌腱韧带损伤9例。结论关节面下囊样骨质破坏、滑膜增厚、关节软骨侵蚀是透析相关性淀粉样变骨关节病的特征性表现,X线平片是观察透析相关性淀粉样变骨关节病患者骨关节改变的基本方法,CT和MR是X线平片的重要补充。     

Serum levels of beta 2-microglobulin in various types of hemodialysis

beta 2-microglobulin (beta 2 m) is the major constituent of amyloid fibrils in dialysis-related amyloidosis (DRA), which is considered to be one of the most severe adverse effect of long-term dialysis. In this study we evaluated the efficiency of beta 2 m removal during different dialysis procedures. A total of 45 patients undergoing hemodialysis were divided in five groups: cuprophane dialysis (n = 10), high-flux polysulphone dialysis (n = 10), postdilutional hemodiafiltration (n = 10), conventional postdilutional hemofiltration (n = 10) and predilutional on-line hemofiltration (n = 5). Serum level of beta 2 m was determined before and after different procedures using ELISA. In the group of patients on cuprophane dialysis was registered an elevation of beta 2 m and of 16.8 +/- 11.4% on the average. Serum level of beta 2 m was decreased following all other procedures on the average of 40.7 +/- 16.4% after high-flux polysulphone dialysis, 42.0 +/- 13.7% after conventional hemofiltration, 64.7 +/- 9% after hemodiafiltration and 67.9 +/- 10.1% after predilutional hemofiltration. The best removal of serum beta 2 m was realized by predilutional hemofiltration. Also, we have noticed that patients treated with high-flux synthetic membranes in the longer time-period have lower predyalisis value of beta 2 m compared to patients treated with cuprophane membrane. Further long-term studies will be necessary to conclude whether these procedures could be successful prophylactic and/or therapeutic regimen for dialysis-related amyloidosis.     

Diagnostic imaging for the study of popliteal masses in dialyzed patients

A new type of amyloidosis, secondary to the massive deposition of beta 2-microglobulin, has been identified which is peculiar to long-term (greater than or equal to 5 years) hemodialysis. Popliteal masses have recently been described as a possible manifestation of this type of amyloidosis. We report the results of a clinical-radiologic study of the popliteal region in 28 patients (14 males, 14 females; age 52.9 +/- 12.6 years) undergoing chronic hemodialysis for 60-212 months (mean 127 +/- 40). We aimed at determining the role of diagnostic imaging (conventional radiography, ultrasonography, Computed Tomography) in this pathologic condition. Clinics detected popliteal masses in 4 patients (bilateral in 1). US allowed 2 more cases to be detected and demonstrated the cystic nature of the lesion. Ultimately, popliteal masses could be demonstrated in 6 (bilateral in 5) of 28 patients (incidence 21.4%). In the 3 patients who were investigated by CT, cysts were seen to communicate with the joint cavity (Baker's cysts). In 1 case, immunocytochemical analysis showed diffuse beta 2-microglobulin positive amyloid deposition within the synovial wall of the surgically removed cyst. All the 6 patients experienced some of the major features of dialysis-related amyloidosis: carpal tunnel syndrome (6 cases), destructive arthropathy (5 cases), carpal and shoulder bone radiolucencies (5 and 4 cases, respectively). These findings, while documenting the high prevalence of popliteal cysts among long-term hemodialysis patients and the strong correlation with dialysis-related amyloidosis, stress the importance of diagnostic imaging in the detection and follow-up of such lesions.     

Use of echography for the diagnosis of joint amyloidosis in dialyzed patients

Amyloid arthropathy is an important complication of long-term hemodialysis. This condition may lead to destructive bone lesions and to severe functional impairment. We studied with sonography of both knees 32 long-term dialysis patients (mean dialytic age: 69.7 months), whose 7 were carrying palpable joint swellings. In 29/32 patients, ultrasound scans were associated with knee X-rays films, patellar views included. In one case, opaque arthrography was performed too. Sonography demonstrated the presence of fluid collections within the articular space and the synovial cavities in 19/32 patients (59%). Their content was transonic or mildly hypoechoic. X-ray films were positive for amyloid bone involvement in 19/29 cases (66%), with intra-osseous cysts and cortical erosions. There was a good general agreement between the results obtained with the two techniques: therefore, in some cases only one examination was positive. Sonography is proposed, in association with standard X-ray films, as a simple and reliable method for the diagnosis of articular amyloidosis in dialysis patients and for the follow-up of this disease.     

Imaging of renal osteodystrophy

Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.     

Carpal cysts in hemodialysis patients

A new type of amyloidosis due to beta 2-microglobulin depositions has been recently described in long-term hemodialysis patients. This systemic complication mainly affects the osteoarticular system, with diffuse articular symptoms; among them carpal tunnel syndrome is the most frequent. The syndrome etiopathology is unknown, even though many causal factors have been identified, among which the repeated use of non-biocompatible dialytic membranes. The authors conducted a retrospective study of 138 hemodialysis patients, with mean dialytic age of 79.3 months, to evaluate both incidence and evolution of bone cysts involving the carpal bones. Bone cysts were detected in the hands of 18.8% of the patients at the beginning of dialytic treatment; their incidence was over 50% after 10 years of treatment. Their size and number showed a rapid progression after the 6th year of hemodialysis, and their features were not related to osteodystrophic bone lesions. The carpal tunnel syndrome appeared after several years and its incidence was 7.9%; a direct correlation was demonstrated with the size of carpal bone cysts. The influence of hemodialysis membrane type on the occurrence of hemodialysis-related amyloidosis was strong, but not exclusive.     

Osteoarticular amyloidosis caused by dialysis

The accumulation of amyloid in the bone and joint system has recently been recognized as a peculiar disease in patients undergoing long-term hemodialysis (5 years at least), especially in those who use cuprophan membranes. The pathology of amyloidosis is characterized by deposits of amyloid (beta 2-microglobulin mainly) in the bone, in the synovia, and in pericapsular soft tissues. The skeleton of 46 long-term hemodialysis patients (19 males and 27 females) was studied by X-ray: bone and joint abnormalities due to amyloid deposition were observed in 45% of cases. The shoulder, hip, and wrist were the most frequently involved joints. Destructive spondyloarthropathy was present in 15% of cases. The radiographic patterns of AOD are generally divided into axial and peripheral lesions. In the appendicular skeleton abnormalities include: well-defined lytic areas (geodes), pathologic fractures, marginal erosions, and periarticular soft tissue swelling. Destructive spondyloarthropathy is frequently present in the cervical spine (85% of our cases), and is characterized by narrowing of the intervertebral space, marginal erosion, and subchondral bone sclerosis of the vertebral body.     

Radiologic and clinical aspects of osteoarticular amyloidosis caused by dialysis]

Many long-term (greater than 60 months) hemodialysis patients develop a severe osteoarticular disease, called "dialysis arthropathy", which is characterized by the deposition in bone and synovia of a new type of amyloid made mainly of beta 2-microglobulin. In the present study, 31 patients (17 males, 14 females; age 54.1 +/- 13 years), undergoing chronic hemodialysis for 60-125 months, were examined for dialysis arthropathy by means of clinics and of radiological investigations (conventional radiography and computed tomography). Sixteen patients (51.6%) had radiographic evidence of dialysis arthropathy: geodes (shoulders, 12 cases; wrists, 11; hips, 2; knees, 2) and/or destructive arthropathies (cervical spine, 13 cases, dorsolumbar spine, 2; hands, 2; hips, 1). Within 24 months, these lesions were found to progress slowly in the majority of cases. In the diagnostic process, CT should be employed in the study of spine, shoulders and hips when the lesions have not been sufficiently demonstrated by conventional radiography in the presence of evident clinical signs. Patients with dialysis arthropathy had undergone dialysis for longer periods than those without it (p less than 0.005) and showed a significantly higher incidence of both carpal tunnel syndrome (p less than 0.0005) and shoulder pain (p less than 0.005). Our findings confirm the high incidence and clinical importance of dialysis arthropathy in long-term hemodialysis patients and the value of diagnostic imaging in screening such patients for those lesions.     

Shoulder arthropathy in primary hyperparathyroidism

An erosive arthropathy of the hands and wrists has been recognized in patients with primary and secondary hyperparathyroidism [3, 5]. Recently, intra-articular erosions of the humeral head were described in six patients who had been on chronic long-term hemodialysis with secondary hyperparathyroidism [1]. We would like to present the finding of shoulder erosions in four patients with primary hyperparathyroidism and one patient with renal osteodystrophy and suggest that the humeral erosion can occur in both an intra-articular and peri-articular location.     

Magnetic resonance imaging of dialysis-related amyloidosis of the shoulder and hip

 Objective. The purpose of this study was to evaluate the usefulness of MRI in identifying abnormalities of the periarticular structures in patients with symptoms of dialysis-related amyloid arthropathy. Design and patients. MR images of shoulders and hips in 5 dialysis patients with symptoms of amyloid arthropathy were compared to images of shoulders and hips in 4 asymptomatic dialysis patients, shoulders in 9 nondialysis patients, and hips in 12 nondialysis patients. These were evaluated for the presence of focal periarticular osseous lesions, tendinous and capsular thickening, and periarticular fluid. Results. Increased thickness of the supraspinatus tendon was found in both symptomatic and asymptomatic patients. Capsular thickening at the hip was present in all symptomatic patients, and in 3 of 8 asymptomatic hips. Joint and bursal fluid was common in the symptomatic group, and was present in some asymptomatic individuals. Osseous lesions were detected in the absence of plain film findings, and demonstrated variable signal intensity. Conclusions. MRI is useful in detecting signs of dialysis-related amyloidosis. Findings of a milder degree in asymptomatic dialysis patients suggests that MRI may also be valuable in the early diagnosis of this syndrome.     

Osteoarthropathy of the hand and wrist in patients undergoing long-term hemodialysis

Radiographs of the hand and wrist in 81 patients who had undergone hemodialysis for a minimum of 5 years (mean, 7.8 years) were reviewed. In 32 patients arthritic changes were found, consisting of articular erosions, joint space narrowings, periarticular cysts, and osteopenia. Seven of the 32 patients had periarticular calcific deposits. The frequency and severity of the radiographic findings increased with increasing duration of dialysis. It appears that in addition to the well-recognized secondary hyperparathyroidism there is another commonly occurring osteoarthropathy (40% in this series) related to long-term hemodialysis.     

Amyloid arthropathy of the hip joint: MR demonstration of presumed amyloid lesions in 152 patients with long-term hemodialysis

The aim of this study was to determine the spectrum of MR findings of presumed amyloid arthropathy of the hip joints in patients on long-term hemodialysis. We prospectively performed T1- and T2-weighted spin-echo imaging on 152 consecutive patients on hemodialysis. The duration of hemodialysis ranged from 5 months to 24 years, 2 months (mean: 8 years, 8 months). The frequency, location, and signal intensity of bone lesions were assessed. In 12 cases with contrast-enhanced MR examination, enhancement pattern of bone lesions, synovial lesions, and intra-articular lesions were characterized. Bone lesions presumed to be amyloid deposits were identified in 60 patients (39 %). Magnetic resonance imaging revealed that amyloid lesions were more extensive than anticipated by plain radiographs. All bone lesions showed decreased signal intensity on T1-weighted images. On T2-weighted images, bone lesions showed increased signal intensity in 32 patients (54 %), decreased signal intensity in 11 patients (18 %), and both increased and decreased signal intensity in 17 patients (28 %). Following intravenous injection of gadolinium-based contrast, all bone lesions showed moderate enhancement. Synovial thickening could not be identified on T1- and T2-weighted images. However, contrast-enhanced images showed thickened synovial membrane, which could be differentiated from joint fluid. Intra-articular nodules showed decreased or intermediate signal intensity on T1-weighted images and decreased signal intensity on T2-weighted images; the intra-articular nodules were contiguous with subchondral bone lesions. Magnetic resonance imaging is useful for evaluating the distribution and extent of amyloidosis of the hip joints in patients undergoing long-term hemodialysis. Received 5 August 1997; Revision received 22 October 1997; Accepted 11 February 1998     

Shoulder erosions in renal osteodystrophy

The radiographic manifestations of renal osteodystrophy may be articular as well as osseous. The latter are well recognized, i.e., subperiosteal and subchondral bony resorption. Recently attention has been directed to the occurrence of an erosive arthritis of the hands and wrists in hyperparathyroidism. The authors present six patients with humeral head erosions, all of whom were on chronic long-term hemodialysis. These intra-articular erosions occurred at the bare area of the humeral head and thus represent an erosive arthritis and therefore can be distinguished from the usual sites of subchondral and subperiosteal bony resorption seen in hyperparathyroidism.     

Bone cysts and haemodialysis-related amyloidosis

Carpal tunnel syndrome and arthropathy are frequent complications of long-term haemodialysis. Both are associated with cystic lesions of bone and are related to synovioarticular deposition of a new type of amyloid derived from circulating beta 2-microglobulin. Retrospective analysis of the radiographic skeletal surveys of all 58 patients on haemodialysis for 6 or more years revealed one or more cystic bone lesions in 36% of patients. Radiographic analysis indicated that a number of these cysts were due to hyperparathyroid bone disease or joint degeneration, but a majority showed features suggesting an arthropathy of another aetiology. We present evidence that the development of these latter cysts in an individual on long-term dialysis is an indicator of the presence of synovioarticular amyloidosis of the beta 2-microglobulin type. The radiographic characteristics and development of these cysts, which we believe are due to bony infiltration from synovioarticular amyloid are described.     

Amyloid tumor in a patient on a regular hemodialysis program]

Amyloidosis is frequent complication in the patients subjected to hemodialysis, and is most frequently manifested in carpal tunnel syndrome, scapulohumeral periarthritis, osseous cysts and exceptionally as solitary tumor. A patient in presented, aged 72 years, who had undergone chronic dialysis for 10 years, in the last 4 years with symptoms and signs of amyloidosis, such as scapulohumeral periarthritis and erosive arthritis of the knee with recurrent effusions. A year ago he had noticed a tumor in the left popliteal cavity that had been progressively increasing and had limited the movements of the knee. After the extirpation, the diagnosis of amyloid tumor was confirmed by histopathologic analysis.     

Annual evaluation of hip joints and hands for radiographic signs of Aβ2M-amyloidosis in long-term hemodialysis patients

Radiographs of hand and hip joints of 15 hemodialysis patients taken annually over at least 15 years were evaluated in this retrospective study. We looked for signs of A₂M-amyloidosis such as lucencies, erosions, and soft tissue swelling. The femoral head-soft tissue distance (FHSTD) was used to estimate the soft tissue swelling of the hips. The number and size of lucencies, the number of erosions, and the FHSTD increased during dialysis. Both hyperparathyroidism and failure of renal allograft transplantation influenced the development of lucencies and erosions after 15 years. The FHSTD at the start of the dialysis appeared to be an independent prognostic factor for the lucencies of the hips and hands. We conclude that the radiological signs of A₂M-amyloidosis are influenced not only by the duration of dialysis, but also by age, failure of renal transplantation, hyperparathyroidism and the FHSTD at the start of dialysis.     

Bone scan in chronic dialysis patients with evidence of secondary hyperparathyroidism and renal osteodystrophy.

Bone scans in 13 of 14 patients on chronic dialysis were found to be abnormal. Symmetrical increased activity was noted in the calvarium, mandible, sternum, shoulders, vertebrae, and the distal aspects of the femur and tibia, as well as the patella. The scan abnormality is felt to be most likely the result of secondary hyperparathyroidism because of clinical and laboratory data, and, in four, confirmatory tissue diagnoses. The scan findings support the data of some earlier investigations on bone isotopic accretion in hyperparathyroidism. However, co-existing osteomalacia giving rise to abnormal activity in some of the patients cannot be excluded. Dihydrotachysterol may have minimized the extent of osteomalacia in these patients. Osteoporosis was probably present in some patients, but it appears differently on scan. Osteosclerosis was not detected on radiographic examination. Scan manifestations, especially mandibular activity, were pronounced and appeared earlier than the radiographic changes. The degree and extent of abnormal activity correlated with the length of dialysis and the level of alkaline phosphatase.     

Atypical rapid progression of osteoarticular amyloidosis involving the hip in a patient on hemodialysis using polyacrylonitrile membranes

Amyloidosis related to dialysis is a well-known complication affecting many organ systems, in particular the musculoskeletal system. In 1985 Shirahama et al. (Biochem Biophys Res Commun 53:705-709, 1985) identified beta-2 microglobulin (MG) as the offending constituent by using protein purification techniques. Amyloidosis has been increasing in prevalence because of longer life spans and increased chronic medical conditions such as end-stage renal disease. When dialysis-related amyloidosis involves the musculoskeletal system, it affects the shoulder girdle, the so called shoulder pad sign, the wrist, hip, knee, and spine (Resnick, Diagnosis of bone and joint disorders, 4th edn., pp. 2054–2058 and 2176–2183, 2002). Other osteoarticular manifestations of amyloidosis include osteoporosis, lytic lesions, and pathologic fractures. It has been well documented that the prevalence of amyloid is dependent on duration of dialysis—over 90% in patients on dialysis for over 7 years (Jadoul, Nephrol Dial Transplant 13:61–64, 1998). However, a recent changeover to high-flux membranes used in hemofiltration has been reported to delay its onset (Campistol et al., Contrib Nephrol 125:76-85, 1999). We report on the radiographic, nuclear medicine, and computed tomography (CT) findings of osteoarticular amyloidosis involving the hip, and sequence its atypical rapid onset. The imaging, histopathological findings, and differential diagnosis are discussed.     

Dialysis-related amyloidosis

Dialysis-related amyloidosis (DRA) is a well-recognized complication in patients on long-term hemodialysis. It occurs secondary to the deposition of beta(2)-microglobulin, preferentially in the musculoskeletal tissues. Plain radiography demonstrates advanced DRA findings such as bone erosions and cystic lesions, but it is not suitable for the demonstration of earlier changes. Magnetic resonance imaging and ultrasound are sufficient for the detection of amyloid deposition in the periarticular soft tissues and in the evaluation of spinal complications.