AL amyloid vs AA and ATTR amyloid
How to tell AL amyloid and AA and ATTR amyloid apart when a board question makes them look alike.
AL is light chain/plasma cell; AA is chronic inflammation/SAA; ATTR is transthyretin cardiac-neuropathic amyloid.
Side by side
AL amyloid is immunoglobulin light-chain amyloid from plasma-cell dyscrasia such as multiple myeloma, often affecting heart, kidney, nerves, and tongue.
AA amyloid derives from serum amyloid A in chronic inflammation; ATTR derives from transthyretin, causing hereditary or senile cardiac/neuropathic amyloidosis.
Misfolded monoclonal light chains deposit as beta-pleated sheets in tissues.
Chronic inflammation elevates SAA leading to AA; transthyretin misfolding causes ATTR deposition.
Plasma-cell disorder, monoclonal protein, macroglossia, and Congo red apple-green birefringence support AL.
Chronic inflammatory disease supports AA; restrictive cardiomyopathy or neuropathy in older/hereditary context supports ATTR.
The trap
All amyloid stains Congo red, so precursor protein and clinical context separate types.
The repair move
For amyloidosis, identify the precursor protein before naming the syndrome: (1) AL amyloid (light chain, primary amyloidosis): immunoglobulin LIGHT CHAINS from monoclonal plasma cells (multiple myeloma, MGUS); presents with NEPHROTIC syndrome, restrictive cardiomyopathy with low-voltage ECG plus thick walls on echo, hepatomegaly, macroglossia, periorbital purpura (the high-yield 'pinch purpura' from minor trauma), peripheral neuropathy and autonomic neuropathy; confirm with serum and urine free light chain assay plus tissue biopsy (fat pad, rectum, kidney) showing Congo red apple-green birefringence under polarized light; treat with bortezomib-based chemotherapy plus autologous stem cell transplant. (2) AA amyloid (secondary amyloidosis): SERUM AMYLOID A acute-phase protein from chronic inflammation (rheumatoid arthritis, inflammatory bowel disease, familial Mediterranean fever, chronic infections like TB and osteomyelitis); presents mainly with NEPHROTIC syndrome and proteinuria; treat the underlying inflammation. (3) ATTR amyloid: TRANSTHYRETIN (prealbumin) deposits; wild-type ATTR (senile cardiac amyloid) in elderly men with restrictive cardiomyopathy and carpal tunnel syndrome; hereditary ATTR (transthyretin mutation, classic in West African and Portuguese populations) presents with cardiac amyloid plus peripheral neuropathy; treat with tafamidis (TTR stabilizer) or patisiran (TTR siRNA gene silencer). (4) Beta-2 microglobulin amyloid: in long-term dialysis patients, deposits in carpal tunnel and joints.
Try a free question
CoreA 64-year-old woman has 6 months of nephrotic-range proteinuria (8 g/day), heart failure with markedly elevated NT-proBNP, hepatomegaly, and easy bruising including periorbital purpura. SPEP shows an IgG kappa monoclonal protein. Bone marrow biopsy shows 18% clonal plasma cells. Kidney biopsy shows apple-green birefringence on Congo red stain. Which type of amyloidosis is most likely?
Show answer and explanation
Answer: A. AL amyloidosis (immunoglobulin light chain). AL amyloidosis is caused by deposition of immunoglobulin light chains produced by clonal plasma cells; multisystem involvement (heart, kidneys, liver, soft tissues, GI) with characteristic 'raccoon eyes' periorbital purpura is classic; treatment is plasma cell-directed chemotherapy.
Why the other choices are tempting
- B. AA amyloidosis is deposition of serum amyloid A from chronic inflammation (RA, IBD, chronic infections).
- C. ATTR amyloidosis is from transthyretin (wild-type or mutant) producing cardiac and neuropathic disease.
- D. Beta-2 microglobulin amyloidosis occurs in patients on long-term hemodialysis with carpal tunnel and joint involvement.
- E. Hereditary cystatin C amyloidosis is a rare cerebrovascular form.
Flashcards
Tap a card to flip it.
What stain supports amyloid?
Congo red with apple-green birefringence supports amyloid.
What precursor causes AA amyloid?
Serum amyloid A causes AA amyloid.
Quick answers
What is the fastest way to tell AL amyloid from AA and ATTR amyloid?
AL is light chain/plasma cell; AA is chronic inflammation/SAA; ATTR is transthyretin cardiac-neuropathic amyloid.
What is the key clue for AL amyloid?
AL amyloid is immunoglobulin light-chain amyloid from plasma-cell dyscrasia such as multiple myeloma, often affecting heart, kidney, nerves, and tongue.
What is the key clue for AA and ATTR amyloid?
AA amyloid derives from serum amyloid A in chronic inflammation; ATTR derives from transthyretin, causing hereditary or senile cardiac/neuropathic amyloidosis.
What is the common trap with AL amyloid vs AA and ATTR amyloid?
All amyloid stains Congo red, so precursor protein and clinical context separate types.