1. The Amyloidoses
Douglas A. Stahura
4/7/99

2. Amyloidoses History
Virchow described a homogenous eosinophilic material which binds Congo red stain.
Associated with inflammatory joint disease and amyloid deposition in kidney, liver, spleen.

3. Amyloidoses Definition
Criteria for definition
Homogenous, hyaline eosinophilic on H+E stain
Crystal violet metachromasia
Stains with alkaline Congo red
Apple green birefringence on polarized light
Fibrillar structure on microscopy
Salt extraction yields p-component forms
Fibril is unique for all forms of amyloid

4. Amyloidoses AL L-chain primary, MM AH H-chain primary, MM
ATTR transthyretin senile systemic
Abeta2M Beta2 microglobulin dialysis
Abeta beta-protein precursor Alzheimer
Ascr Scrapie Creutzfeldt-Jakob

5. Amyloidoses
Most common clinical form beta protein placque of Alzheimer’s
for rheumatoligist AL disease primary amyloidoses or MM

6. Amyloidoses Clinical Presentation
Renal: nephrotic range protenuria or mild
must be distinguished from monoclonal light chains
protein may diminish with renal insufficiency
HTN
Enlargement occurs early

7. Amyloidoses Clinical Presentation
Cardiac: Restrictive cardiomyopathy- noncompliant hemodynamics, thickening of septum
on Echo- “sparkling” of echoes
endomyocardial biopsy shows AL deposition on immunohistochemical staining
Digoxin and Nifedipine toxicity reported due to collective binding to fibrils.

8. Amyloidoses Complication
AL disease - acquired deficiency of clotting factor X
Periarticular amyloid deposition presenting as pseudoarthritis = shoulder pad sign

9. Amyloidoses Treatment
Melphalan and Prednisone
2 controlled trials with no statiscally significant improvement in survival
20% of patients did have improvement

10. Amyloidoses B2 Microglobulinemia
significant articular presentation with chronic renal disease
all reported pt’s presented with
joint pain
carpal tunnel
osteonecrosis
dialysis for mean of 7 years
B2 microglobulin is polypeptide of class I protein of MHC

11. Amyloidoses AA Amyloid
AA deposition in tissues, associated with
rheumatoid arthritis
familial Mediterranean fever
Recent series 5% of RA have tissue deposits and 2% have cinically evident disease, usually renal or hepatic.
Worldwide, AA deposition common in leprosy, tuberculosis, osteomyelitis.

12. Amyloidoses AA Amyoid
Clinical - episodic fever, arthritis, abdominal/pleuritic inflammation
Treatment - Colchicine
abortive of acute episodes
abortive of amyloid formation

13. Amyloidoses Aging 5 sites identified with aging
Brain: beta protein of Alzheimer’s
Pancreas: islet associated polypeptide
ANF: fibril of isolated atrial amyloid
Cardiac: transthyretin, senile systemic amyloid
Aorta: fibril not identified