Amyloidosis (?musc)

Question 1

Define amyloidosis

Answer 1

Heterogenous group of diseases characterised by extracellular deposition of amyloid fibrils

Question 2

Aetiology/risk factors for amyloidosis

Answer 2

Amyloid fibrils are polymers of low molecular weight subunit proteins derived from proteins that undergo conformational change to adopt anti-parallel β-pleated sheet configuration.

Deposition progressively disrupts structure & function of normal tissue.

Amyloidosis classified by fibril subunit proteins:
Type AA - serum amyloid A protein
Type AL - monoclonal immunoglobulin light chains
Type ATTR (familial amyloid polyneuropathy) - genetic variant transthyretin

Question 3

Epidemiology of amyloidosis

Answer 3

AA: 1-5% patients w/ chronic inflammatory diseases

AL: 300-600 cases in UK per year

Hereditary amyloidosis: 5% of the patients w/ amyloidosis

Question 4

Presenting symptoms & signs of amyloidosis on examination

Answer 4

Renal - proteinuria, nephrotic syndrome, renal failure

Cardiac - restrictive cardiomyopathy, heart failure, arrhythmia, angina

GI - macroglossia (characteristic of AL), hepatosplenomegaly, gut dysmotility, malabsorption, bleeding

Neurological - sensory & motor neuropathy, autonomic neuropathy, canal tunnel syndrome

Skin - waxy skin & easy bruising, purpura around the eyes (characteristic of AL), plaques & nodules

Joints - painful asymmetrical large joints, enlargement of anterior shoulder

Haematological - bleeding tendency

Question 5

Appropriate investigations for amyloidosis (& their results)

Answer 5

• Tissue biopsy
• Urine
  (check for proteinuria, free immunoglobulin light-dark chains in AL)
• Bloods
  (CRP/ESR, rheumatoid factor, immunoglobulin levels, serum protein electrophoresis, LFTs, U&Es)
• SAP scan
  (radio labelled SAP will localised amyloid deposits)