Dialysis-Related Beta-2m Amyloidosis Clinical Presentation

Updated: Feb 03, 2017
  • Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Presentation

History

Clinical manifestations of beta-2m amyloidosis almost never appear before a patient has undergone 5 years of dialysis therapy. Unlike other types of amyloids, beta-2m amyloid is confined largely to osteoarticular sites. [12]

Patients often present with a characteristic triad of carpal tunnel syndrome, shoulder pain, and flexor tenosynovitis in the hands. The rate of surgery for osteoarticular disorders, such as carpal tunnel syndrome, destructive spondyloarthropathy (DSA), and joint arthropathy, which may show the presence of DRA, is very high. [13]

Visceral deposits are rare, occur after 10 or more years of dialysis, and tend not to cause symptoms in most cases.

Osteoarticular manifestations

Osteoarticular manifestations can include the following:

  • Carpal tunnel syndrome
  • Flexor tenosynovitis
  • Scapulohumeral arthropathy
  • Spondyloarthropathy
  • Lytic bone lesions
  • Bone cysts
  • Pathologic fractures - Caused by amyloid deposition within joints, intervertebral discs, and tendon sheaths [12]
  • Musculoskeletal deformities

Carpal tunnel syndrome

This syndrome is the most common presenting feature. It usually is bilateral and progressive. [11] Patients report numbness, paresthesias, pain, and swelling in the region of the distal median nerve. Pain usually is worse during dialysis and at night. Progression to contraction of the hand and atrophy of the muscles can occur. However, it is important to remember that not all cases of carpal tunnel syndrome in dialysis patients are amyloid related; the syndrome may arise from other causes, such as ischemia.

Flexor tenosynovitis

This disorder is often referred to as trigger finger or trigger thumb. Patients can flex the finger, but with reextension, the patient may feel a painful snap that refers to the dorsum of the hand.

Scapulohumeral arthropathy

Amyloid may deposit in and around the rotator cuff, resulting in shoulder pain that becomes worse when the patient is in the supine position. Patients often report difficulty dressing.

Spondyloarthropathy

The cervical spine is most often affected, and patients often present with neck and back pain. DSA is a major cause of hospital admissions in long-term dialysis patients, especially in patients who have undergone dialysis for 30 years or more.

Bone cysts

Thin-walled bone cysts are common and are most frequently found in the carpal bones. They are also observed in the femoral heads, humerus, patella, acetabulum, and spine. Patients may experience stiffness and/or pain over the affected area.

Fractures can develop in bones weakened by bone cysts. The femoral neck is most commonly involved. Patients may experience a sudden onset of leg pain while walking.

Systemic manifestations

Systemic manifestations are rare, and patients with systemic involvement generally are asymptomatic. Most individuals with systemic manifestations have undergone dialysis for longer than 10-15 years.

If systemic involvement does occur, small, localized deposits are observed around blood vessels and in the mucosa of the GI tract, heart, lungs, and genitourinary tract. In rare cases, fatal GI hemorrhages, cardiac arrhythmias, and renal vein thromboses have occurred.

GI involvement

Macroglossia, dysphagia, small bowel ischemia, malabsorption, and pseudo-obstruction can occur because of subepithelial, submucosal, and blood vessel amyloid deposits. [14]

Cardiovascular involvement

Myocardial, pericardial, and cardiac valves may be involved. Beta-2m amyloid deposits have also been identified in small pulmonary arteries and veins.

Genitourinary tract involvement

Renal and bladder calculi containing beta-2m deposits and causing obstruction have been described. Beta-2m amyloid has also been identified in the prostate and the female reproductive tract.

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Physical Examination

Systemic involvement is rare in beta-2m amyloidosis. Osteoarticular involvement can include the following:

  • Carpal tunnel syndrome - Patients experience weakness and atrophy of the thenar muscle, along with decreased strength in abduction, opposition, and flexion of the thumb
  • Flexor tenosynovitis - Amyloid deposits may result in prominence of the tendons of the hands on extension; patients often experience decreased digital mobility and soft-tissue swelling over flexor tendon sheaths
  • Scapulohumeral arthropathy - Deposits in and around the rotator cuff may cause soft-tissue thickening around the shoulder, referred to as the shoulder pad sign; the patient's capacity to abduct or internally rotate the arm is limited
  • Spondyloarthropathy - Paravertebral ligaments and intervertebral discs may be destroyed or dislocated, resulting in spinal cord impingement or paraplegia; the cervical spine is most often affected, and patients often present with neck and back pain
  • Bone cysts - Cysts grow in size and number in the wrist, humeral head, hip, and patella; as cysts enlarge, soft-tissue swelling and swollen joints, with subsequent spontaneous tendon rupture and pathologic fracture, may occur (cysts do not regress with renal transplantation)

Hoshino et al validated a clinical staging score to measure the severity of dialysis-related amyloidosis (DRA). [15] Elements of the score are as follows:

  • Polyarthralgia – 3 points
  • Dialysis-related spondyloarthropathy (DRS) – 3 points
  • Trigger finger – 2 points
  • Carpal tunnel syndrome – 2 points

DRA is staged according to the score as follows:

  • Mild (3-4 points)
  • Moderate (5-7 points)
  • Severe (8-10 points)
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