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
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