Amyloidosis

Question 1

Define amyloidosis

Answer 1

• Heterogenous group of diseases characterised by extracellular deposition of amyloid fibrils

Question 2

What are the causes/risk factors of amyloidosis?

Answer 2

• monoclonal gammopathy of undetermined significance (MGUS)
• inflammatory polyarthropathy
• chronic infections
• inflammatory bowel disease
• familial periodic fever syndromes
• Castleman’s disease

Question 3

What are the types of amyloidosis?

Answer 3

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 4

What are the signs and symptoms 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

What investigations are carried out for amyloidosis?

Answer 5

• Serum and urine immunofixation - presence of monoclonal protein
• Tissue Biopsy - positive green birefringence when stained with Congo red
• Urine - check for proteinuria, free immunoglobulin light chains (in AL) - abnormal kappa to lambda ratio
• Bloods
- CRP/ESR
- Rheumatoid factor
- Immunoglobulin levels
- Serum protein electrophoresis
- LFTs
- U&Es
• SAP Scan - radiolabelled SAP will localise the deposits of amyloid
• Bone marrow biopsy - clonal plasma cells