Amyloidosis

Accumulation of insoluble fibrillar proteins that form ß-pleated sheets

Classification of Amyloidosis

Type

Precursor

Causative diseases

Organ systems

("Primary") Most common

Ig light chain (monoclonal)

Light chain disease (A>k) MGUS.WM

Renal, cardiac, Gl, neuro, cutaneous, hepatic, pulmonary, musculoskel. heme

("Secondary")

Serum amyloid (SAA)

Chronic infections: osteo.

TB. empyema, leprosy Inflam: RA. I BD. FMF Neoplasms: renal. HD

Renal. Gl, hepatic, neuro. cutaneous

Hereditary

Transthyretin (TTR). et al.

Mutant proteins

Neurologic, cardiac

Senile

TTR.ANP

Normal proteins; 29 aging

Cardiac, aorta. Gl

AfrM

{Jj-microglobulin

Dialysis-associated ß2m (normally renally excreted)

Musculoskeletal

Organ-specific

p-amyloid protein Peptide hormones et al.

Localized production and processing

Neurologic Endocrine etal.

(Adipud from NEJM 1997.337:898 & 2003:349:583)

Clinical Manifestations of Amyloidosis

System

Manifestations

Amyloid

Renal

Proteinuria or nephrotic syndrome

ALAA

Cardiac

Cardiomyopathy (restrictive & dilated) J QRS amplitude, conduction abnormalities. AF Orthostatic hypotension

AL hereditary.

senile, organ-specific

Gl

Diarrhea, malabsorption, protein loss Ulceration, hemorrhage, obstruction Macroglossia — dysphonia and dysphagia

all systemic

Neurologic

Peripheral neuropathy with painful paresthesias Autonomic neuro - impotence, dysmotility. i BP Carpal tunnel syndrome

hereditary. AL. organ-specific. A(Jjm

Cutaneous

Waxy, nonpruritic papules: periorbital ecchymoses "Pinch purpura" = skin bleeds with minimal trauma

AL

Hepatic & Splenic

Hepatomegaly, usually without dysfunction Splenomegaly, usually without leukopenia or anemia

all systemic

Endocrine

Deposition with rare hormonal insufficiency

organ-specific

Musculoskel

Arthralgias and arthritis

ALAfrm

Pulmonary

Airway obstruction

ALAA

Hematologic

Factor X deficiency

• Abdominal SC fat pad or rectal biopsy • apple-green birefringence on Congo red stain

• If suspect renal involvement: / U/A (proteinuria)

• If suspect cardiac involvement: / ECG (. voltage, conduction abnormalities) &

echocardiogram (biventricular thickening with "granular sparkling" appearance)

• Genetic testing for hereditary forms

Treatment

• ALmelphalan • prednisone (NEjm 1997:336:1202). ? iododoxorubicin. ? stem cell transplant

• AA: treatment of underlying disease

Familial Mediterranean Fever: colchicine [NEjm 1986:314 lOOl)

• For hereditary amyloidoses in which amyloid precursor protein is produced by the liver (eg.TTR). liver transplantation may prevent further deposition

• Heart, kidney, and liver transplantation may be considered in those with advanced disease

Prognosis

• AL amyloid: median survival 12-18 mos; if cardiac involvement, median survival 6 mos

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