Amyloidosis

Background

• Amyloidoses are a group of acquired and hereditary disorders characterised by extracellular deposition of insoluble proteins, which can be localised or systemic
  • Clinical presentation depends on the organs involved

Types

• Reactive (AA) amyloidosis
  • Increased production of serum amyloid A as part of prolonged or recurrent acute inflammatory response
    • e.g. Chronic infection (TB, bronchiectasis, chronic abscess, osteomyelitis); Chronic inflammatory disease (chronic untreated/poorly controlled rheumatoid arthritis; familial Mediterranean fever)
  • Most patients present with non-selective proteinuria or nephrotic syndrome
  • May also have hepatosplenomegaly
  • On investigations there may be signs of hepatorenal problems e.g. raised urea and low serum albumin
• Light Chain amyloidosis (AL)
  • Increased production of monoclonal light chains
    • e.g. monoclonal gammopathies e.g. myeloma, benign gammopathies and plasmacytoma
  • Presents with features of restrictive cardiomyopathy, peripheral neuropathy/autonomic neuropathy, carpal tunnel syndrome, proteinuria, spontaneous purpura, amyloid nodules and plaques
    • Macroglossia occurs rarely but is pathognomonic
  • Prognosis is often poor
• Dialysis associated (Aβ2M) amyloidosis
  • Accumulation of circulating β2 microglobulin due to failure of renal catabolism in renal failure
    • associated with dialysis / renal failure
      • often 5-10 years from start of dialysis
  • Presents with carpal tunnel syndrome, chronic arthropathy and pathological fractures due to amyloid bone cysts formation
• Senile systemic amyloidosis
  • Normal deposition of transthyretin protein in tissues in older patients (>70)
    • Normal process of aging
    • Usually asymptomatic
• Hereditary systemic amyloidosis
  • Multiple forms – many mutations of the transthyretin gene; often autosomal dominant
  • Peripheral and autonomic neuropathy, cardiomyopathy (renal involvement is unusual- ~10%)
    • Many asymptomatic

Presentation

• Amyloidosis should be considered in all cases of unexplained nephrotic syndrome, cardiomyopathy and peripheral neuropathy

Investigation/Diagnosis

• Biopsy confirms diagnosis (affected organ, rectum or subcutaneous fat)
  • apple-green birefringent amyloid deposits (Congo red dye)
• Quantitative scintigraphy with radiolabelled SAP can estimate total body load

Management

• Largely supportive; prevent further deposition by treatment of any underlying cause, where possible
  • Liver transplantation may be an option