Amyloidosis

Question 1

Define amyloidosis

Answer 1

Disease characterised by extracellular deposition of amyloid (insoluble fibrils)

Amyloid deposit = any histological specimen that binds the cotton wool dye, Congo red, and demonstrates green birefringerence when viewed under polarised light.

Question 2

Types of amyloidosis

Answer 2

Primary (AL) - Ig light chain amyloidosis
Non-familial secondary amyloidosis (AA)
Secondary amyloidosis (AA)
ATTR/familial amyloid polyneuropathy

Question 3

Features of primary amyloidosis

Answer 3

AL amyloidosis - light chains
Unknown aetiology
Associated with plasma cell dyscrasia - Multiple myeloma, B cell lymphoma

Question 4

Features of non-familial secondary amyloidosis

Answer 4

AA amyloidosis
Associated with:
Inflammatory polyarthropathies (60%) e.g. RhA, juvenile A, psoriatic arthritis, ankylosing spondylitis
Chronic infections e.g. Bronchiectasis, SC illicit drug injection, decubitus ulcers, chronic UTI, osteomyelitis
IBD (specifically Crohn’s)
Castleman’s disease

Question 5

Features of secondary amyloidosis

Answer 5

AA amyloidosis
Associated with Familial Mediterranean fever and Muckle-Well syndrome

Question 6

Features of ATTR (familial amyloid polyneuropathy)

Answer 6

Autosomal dominant
Mutation in the gene for transthyretin (TTR)

Question 7

Features of AL vs AA amyloidosis

Answer 7

AL
Proteinuria with and without nephrotic syndrome, plus uraemia – 50% of patients die of renal failure if not treated with dialysis
Visceromegaly (spleen, liver and kidneys) is common

AA
Nephrotic syndrome (one-third of patients)
Neuropathy (usually sensory and symmetrical)
Cardiomyopathy (usually restrictive in nature)
Hepatomegaly
Autonomic neuropathy

Question 8

Clinical features of amyloidosis

Answer 8

General: weight loss, fatigue
Respiratory: dyspnoea on exertion
Cardio: restrictive cardiomyopathy, HF< arrhythmias
Gastrointestinal system: macroglossia, malabsorption or hepatosplenomegaly, nausea, abdo cramps, alternating bowel habit
Kidneys: nephrotic syndrome/renal failure → Lower limb swelling
Neurological system: neuropathies and paraesthesia
Vasculature: periorbital purpura (“racoon eyes”), claudication
Joints: painful asymmetrical large joint inflammation
Haematological: Bleeding diathesis

Question 9

Investigations for amyloidosis

Answer 9

Urine immunofixation: Presence of monoclonal protein (+ve in 60% with AL)
Urine dip: Proteinuria
ECG: ?cardiac function

Ig free light chain assay: Abnormal kappa to lambda ratio (AL)
Serum immunofixation: monoclonal protein
CRP/ESR
Rheumatoid factor
IG levels
Serum protein electrophoresis
LFTs
U&Es
BNP

Tissue biopsy (usually rectum): Positive apple-green birefringence when stained with Congo Red stain under polarise light
BMB
Echo: ?cardiac function
Radio-labelled serum amyloid P scans (SAP

Question 10

Management for amyloidosis

Answer 10

Guided by the National Amyloidosis Centre in London

Supportive:
Reduce amyloid protein
- Autologous BM transplantation in fit individuals
- Hereditary → hepatic transplantation

Monitor and support complications:
- Renal
- GI
- Cardiac
- Bleeding

AA: manage chronic infection and inflammation
AL: strategies similar to myeloma therapy can be used (eg. dexamethasone and bortezomib as a first line) with measurements of serum-free light chains to assess response