Amyloidosis

Question 1

Define amyloidosis

Answer 1

Heterogenous group of diseases characterised by

extracellular deposition of amyloid fibrils

Question 2

Explain the aetiology/risk factors of amyloidosis

Answer 2

Amyloid fibrils are polymers of low-molecular-weight subunit proteins

These are derived from proteins that undergo conformational changes to adopt an anti-parallel beta-pleated sheet configuration

Their deposition progressively disrupts the structure and function of normal tissue

Amyloidosis is classified according to the 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

Summarise the epidemiology of amyloidosis

Answer 3

AA-incidence of 1-5% amongst patients with chronic inflammatory diseases

AL- 300-600 cases in the UK per year

Hereditary Amyloidosis - accounts for 5% of patients with amyloidosis

Question 4

Recognise the presenting symptoms and signs of amyloidosis

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 and motor neuropathy, autonomic neuropathy, carpal tunnel syndrome

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

Joints - painful asymmetrical large joints, enlargement of anterior shoulder

Haematological - bleeding tendency

Question 5

Identify appropriate investigations for amyloidosis

Answer 5

Tissue Biopsy

Urine -check for proteinuria, free immunoglobulin light chains (in AL)

Bloods
CRP/ESR
Rheumatoid factor
Immunoglobulin levels
Serum protein electrophoresis
LFTs
U&Es

SAP Scan - radiolabelled SAP will localise the deposits of amyloid