Disorder characterised by extracellular deposits of misfolded proteins

Aetiology

• Inherited and acquired forms however the cause of amyloid production and its deposition in tissues is unknown
• Over 30 identified causative proteins
• AL amyloidosis is the most common type of systemic amyloidosis in developed countries (although still relatively rare)
• The average age of diagnosed patients is 65 years and fewer than 10% of patients are under 50

Pathophysiology

• Deposition of extracellular amyloid (insoluble protein fibrils) in tissues or organs
• Occurs due to abnormal folding of proteins which then aggregate and become insoluble
  • Breakdown of usual degradation pathways for abnormally folded proteins

Types of amyloidosis

AL - light chain

• Production of abnormal immunglobulin light chains from plasma chains
• Light chains enter the bloodstream and cause amyloid deposits
• Commonly affects heart, bowel, skin, nerves, kidneys
• Age at diagnosis 55-60 years

AA - systemic/ inflammatory

• Associated with systemic inflammation
• Production of acute phase protein - serum amyloid A protein
• Develops in approx. 5% of patients with chronic inflammatory conditions or chronic infections
  • RA, IBD, psoriasis
  • TB, osteomyelitis, bronchectasis