Today we discussed amyloidosis. A few points about this rare, but serious and often multi-systemic condition
Amyloidosis refers to deposition of an altered conformation of a protein into amyloid fibrils that deposit systemically, giving various clinical manifestations depending on which system(s) are involved. One way of classifying amyloidosis is by which protein is forming the amyloid:
AL: amyloid is formed by immunoglobulin light chains or fragment produced by clone of plasma cells. Plasma cell burden is usually low (~5-10%). 10% have multiple myeloma.
AA: amyloid is formed by 'amyloid A protein', an acute phase reactant. This form of amyloid is associated with longstanding inflammatory conditions. Classic ones are RA, IBD, FMF
Familial amyloidosis: proteins forming amyloid are transthyreitin, apolipoproteins, lysozyme, etc.
"Senile systemic": transthyreitin amyloid, predominantly in heart.
Others: Alzheimer's disease is associated with amyloid fibril deposition in the brain; the protein is a-beta 40 and 42. It is unclear whether amyloid fibrils are causitive.
Possible clinical manifestations:
1) Neurological- CNS- intracranial hemorrhage (amyloid angiopathy), dementia. PNS- peripheral neuropathy (glove-stocking), compressive neuropathy (e.g. carpal tunnel)
2) Cardiac- infiltrative cardiomyopathy- systolic or diastolic dysfunction, arrhyhtmia (heart blocks or ventricular arrhythmias). Cardiac involvement carries the worst prognosis. Rare in AA amyloidosis.
3) Renal- may cause nephrotic syndrome or asynptomatic proteinuria
4) GI- hepatomegaly with or without splenomegaly, GI bleeding, dysphagia
5) MSK- macroglossia as shown above, arthritis
6) Dermatologic- ecchymoses from friable vessels, periorbital purpura, fat infiltration is common but asymptomatic- may allow for diagnosis
7) Hematologic- Factor X deficiency leading to bleeding diathesis, petechiae (F10 binds to amyloid fibrils)
8) Pulmonary- less common; persistent pleural effusions
Diagnosis is made by organ system involved. Abdominal fat pad bx (stained for Congo red) is positive in 80% of AL, 65% of AA.
Treatment depends on type.
In AA, directed at underlying inflammatory disorder
In AL, directed at underlying plasma cell disorder
For cardiac amyloidosis, implanted defibrillator is sometimes indicated. High dose systemic chemotherapy (e.g. melphalan) is sometimes used.
Link:
2) Cardiac- infiltrative cardiomyopathy- systolic or diastolic dysfunction, arrhyhtmia (heart blocks or ventricular arrhythmias). Cardiac involvement carries the worst prognosis. Rare in AA amyloidosis.
3) Renal- may cause nephrotic syndrome or asynptomatic proteinuria
4) GI- hepatomegaly with or without splenomegaly, GI bleeding, dysphagia
5) MSK- macroglossia as shown above, arthritis
6) Dermatologic- ecchymoses from friable vessels, periorbital purpura, fat infiltration is common but asymptomatic- may allow for diagnosis
7) Hematologic- Factor X deficiency leading to bleeding diathesis, petechiae (F10 binds to amyloid fibrils)
8) Pulmonary- less common; persistent pleural effusions
Diagnosis is made by organ system involved. Abdominal fat pad bx (stained for Congo red) is positive in 80% of AL, 65% of AA.
Treatment depends on type.
In AA, directed at underlying inflammatory disorder
In AL, directed at underlying plasma cell disorder
For cardiac amyloidosis, implanted defibrillator is sometimes indicated. High dose systemic chemotherapy (e.g. melphalan) is sometimes used.
Link:
Click here for a NEJM case discussion of amyloidosis- nicely summarizes the issues
Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases. These are enzymes (EC 3.2.1.17) that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins. lysozyme
ReplyDelete