The Amyloidoses Douglas A. Stahura 4/7/99

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.

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

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

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

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

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.

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

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

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

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.

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

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