Amyloidosis

Question 1

Define amyloidosis?

Answer 1

heterogenous group of disease characterised by extracellular deposition of amyloid fibrils

deposition may be localised or part of systemic deposition

Question 2

what are the risk factors for amyloidosis?

Answer 2

• inflammatory arthropathy
• chronic infections eg bronchiectasis
• IBD especialy crohns

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

outline the aetiology of amyloidosis?

Answer 4

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

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 can be systemic (generalised) or localised, e.g. in pancreatic islets of Langerhans (T2DM), cerebral cortex (Alzheimer’s), cerebral blood vessels (amyloid angiopathy), and in bones and joints.

Question 5

what are the 3 types of amyloidosis?

Answer 5

Type AA - serum amyloid A protein

Type AL - monoclonal immunoglobulin lightchains

Type ATTR (familial amyloid polyneuropathy)- genetic-variant transthyretin

Question 6

how is amyloidosis classified?

Answer 6

according to fibril subunit proteins

Question 7

describe type AL amyloidosis?

Answer 7

monoclonal immunoglobulin lightchains

Also known as primary amyloidosis

Affects kidneys, heart, nerves, gut, vascular

Question 8

describe type AA amyloidosis?

Answer 8

serum amyloid A protein

Also known as secondary amyloidosis (reactive systemic amyloidosis)- depos in chronic inflam conditions such as Crohn’s

Affects kidneys, liver and spleen

Question 9

Describe type ATTR amyloidosis?

Answer 9

Type ATTR (familial amyloid polyneuropathy)- genetic-variant transthyretin

Also known as familial amyloidosis

Usually causes a sensory or autonomic neuropathy +/- renal or cardiac involvement

Question 10

what are the presenting symptoms and signs of amyloidosis?

Answer 10

Renal - proteinuria, nephrotic syndrome (=>oedema), renal failure

Cardiac - restrictive cardiomyopathy, heart failure, arrhythmia, angina, JVP raised=> fatigue + weight loss + dyspnoea, claudication

GI - macroglossia(characteristic of AL – most specific finding), hepatosplenomegaly, gut dysmotility, malabsorption, bleeding=>N, abdo cramps, altered bowel motility

Neurological - sensory and motor neuropathy, autonomic neuropathy, carpal tunnel syndrome => paraesthesia, tinel’s and phalen’s sign

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 11

what are the appropriate investigations for amyloidosis and interpret the results?

Answer 11

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

Bloods

• CRP/ESR
• Rheumatoid factor
• Immunoglobulin levels – presence of monoclonal protein
• Serum protein electrophoresis
• LFTs
• U&Es

Bone Marrow Biopsy – clonal plasma cells seen

Apple green birefringence under polarised light with Congo red stain

Question 12

what investigations would you consider for amyloidosis?

Answer 12

• Tissue Biopsy – to diagnose amyloidosis and identify amyloid fibril protein
• Mass-spec to confirm protein type of amyloid proteins
• Genetic testing – to see if familial cause of amyloidosis
• SAP Scan - radiolabelled SAP will localise the deposits of amyloid
• ECG – to see extent of cardiac involvement
• Echo – to see extent of cardiac involvement