Amyloidosis

Question 1

What is amyloidosis?

Answer 1

A rare disease that results from the build of misfolded proteins called amyloids. Normally proteins are soluble in water, but when misfolded cannot be disolved & get deposited on organs - disrupting their function. (type of misfolded protein & organ deposition determines clinical manifestation)

Question 2

Primary Amyloidosis (AL) - features (3)

Answer 2

Most common, assc with plasma cell dyscrasias & paraproteins e.g. MM - most dont have MM though. Most have monoclonal Ig, free light chains in serum & Urine (BJ proteins) & increased BM plasma cells

Question 3

Secondary (AA) amylodosis: features (3)

Answer 3

Here the amyloid is formed from serum amyloid A - which is an acute phase protein, hence secondary to chronic infections/inflammation:

1. autoimmune diseases - e.g. IBD, RA
2. chronic infections e.g. TB
3. non-immune e.g. RCC, Hodgkin’s

Question 4

Cardinal feature of Haemodialysiss assc amyloidosis (1)

Answer 4

Deposition of beta2-microglobulin

Question 5

Familial amyloidosis - several types, all rare. What is the most common type?

Features of most common type (3)

Answer 5

Most common - Familial mediterranean fever (AR)

• very high IL-1 > attacks of fever & inflammation of serosal surfaces (pleura, peritoneum etc.)
• assc gene encodes pyrin

Question 6

Clinical features of amyloidosis - due to amyloid deposits in various organs (4)

Answer 6

• Kidney - nephrotic syndrome - most common presentation
• Heart - conduction defects, HF
• Tongue - macroglossia (10%)
• Liver - hepatosplenomegaly
• neuropathies - incl carpal tunnel

Question 7

Amyloidosis: Dx (1)

Answer 7

apple green birefringence with congo red stain (under polarized light) - caused by beta-pleated sheet configuration