Amyloidosis

Question 1

Amyloidosis

Answer 1

Overview
amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid
amyloid is derived from many different precursor proteins
in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P
other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans
the accumulation of amyloid fibrils leads to tissue/organ dysfunction

Question 2

Amyloidosis - Classification

Answer 2

Classification
systemic or localized
further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)

Diagnosis
Congo red staining: apple-green birefringence
serum amyloid precursor (SAP) scan
biopsy of rectal tissue

Amyloidosis is associated with lymphoproliferative disorders

Question 3

Amyloidosis - Associations

Answer 3

Amyloidosis may be associated with lymphoproliferative disorders!

Example Question:
A 72-year-old lady who has a background of multiple myeloma is being investigated for bilateral carpal tunnel syndrome, worsening shortness of breath and oedema. Her investigation results are as follows:

Hb 105 g/l
Platelets 145 * 109/l
WBC 7.2 * 109/l

Ca+ 2.70 mmol/l
Urea 4.3 mmol/l
Creatinine 150 µmol/l

Urine protein >3.5/day

Chest x-ray shows cardiomegaly with fluid overload

What are her symptoms most likely to be due to?
	Membranous nephropathy
	> Amyloidosis
	Heart failure
	Minimal change disease
	Treatment side effects

Amyloidosis may be associated with lymphoproliferative disorders and has clinical features relating to the organs involved: heart failure, nephrotic syndrome with proteinuria. Given her background of multiple myeloma, bilateral carpal tunnel syndrome, heart failure and proteinuria, the answer that accounts for all of this is amyloidosis.

Although this lady has heart failure based on her clinical history and chest x-ray findings, it does not explain all of her symptoms.

Membranous nephropathy is less likely to account for this lady’s symptoms as it tends to be associated with lymphoma or chronic lymphoid leukaemia rather than multiple myeloma. Minimal change disease is most common in children and renal function is usually preserved. This pattern of findings is also unlikely to be associated with treatment.